Osteoarthritis (degenerative joint disease) is the most common form of arthritis. If occurs almost universally in the aged, and results in significant disability in over 20% of patients. Therapy at present is symptomatic rather than specific. Therapeutic intervention to prevent, retard or reverse the disease will depend upon increased knowledge of pathogenic and pathophysiologic factors involved in the disease process. Cartilage changes associated with aging processes must be differentiated from those characteristic of osteoarthritis. The availability of a reproducible experimental animal model of osteoarthritis developed in this laboratory, as well as use of well characterized in vitro organ culture techniques provide opportunity for more intensive investigation of disease mechanisms and directions for experimental therapeutic intervention. Studies utlizing an in vivo experimental model and in vitro culture techniques are designed to compare and contrast normal, aging and osteoarthritic cartilage with respect to 1) qualitative and quantitative metabolism of chondrocyte proteoglycan and collagen; 2) to delineate the role of proteolytic and collagenolytic enzymes; 3) to study the effects of estrogens and related hormonal compounds on cartilage; 4) to study cartilage prostaglandins as they related to enzymatic cartilage degradation, and to proteoglycan and collagen synthesis/repair processes; and 5) to define mechanisms of osteophyte formation. Investigations are directed towards the elucidation of further insights to osteoarthritis and therapy.